1. Field of the Invention
This invention relates to biosensors such as glucose sensors used in the management of diabetes and materials for making such sensors, for example blended polymeric compositions useful for biosensor membranes.
2. Description of Related Art
Analyte sensors such as biosensors include devices that use biological elements to convert a chemical analyte in a matrix into a detectable signal. There are many types of biosensors used to detect wide variety of analytes. Perhaps the most studied type of biosensor is the amperometric glucose sensor, an apparatus commonly used to monitor glucose levels in individuals with diabetes.
A typical glucose sensor works according to the following chemical reactions:
H2O2→O2−2H++2e−  Equation 2
The glucose oxidase is used to catalyze the reaction between glucose and oxygen to yield gluconic acid and hydrogen peroxide as shown in equation 1. The H2O2 reacts electrochemically as shown in equation 2, and the current is measured by a potentiostat. The stoichiometry of the reaction provides challenges to developing in vivo sensors. In particular, for optimal sensor performance, sensor signal output should be determined only by the analyte of interest (glucose), and not by any co-substrates (O2) or kinetically controlled parameters such as diffusion. If oxygen and glucose are present in equimolar concentrations, then the H2O2 is stoichiometrically related to the amount of glucose that reacts at the enzyme; and the associated current that generates the sensor signal is proportional to the amount of glucose that reacts with the enzyme. If, however, there is insufficient oxygen for all of the glucose to react with the enzyme, then the current will be proportional to the oxygen concentration, not the glucose concentration. Consequently, for the sensor to provide a signal that depends solely on the concentrations of glucose, glucose must be the limiting reagent, i. e. the 02 concentration must be in excess for all potential glucose concentrations. A problem with using such glucose sensors in vivo, however, is that the oxygen concentration where the sensor is implanted in vivo is low relative to glucose, a phenomena which can compromise the accuracy of sensor readings.
There are a number of approaches to solving the oxygen deficit problem. One is to make a porous membrane from a fully oxygen permeable material. However, the small amount of enzyme disposed for glucose tends to become inactivated (see, e.g. U.S. Pat. No. 4,484,987, the contents of which are incorporated by reference). Another approach is to use a homogenous polymer membrane with hydrophobic and hydrophilic regions that control oxygen and glucose permeability (see, e.g. U.S. Pat. Nos. 5,428,123; 5,322,063, 5,476,094, the contents of which are incorporated by reference). For example, Van Antwerp et al. have developed linear polyurea membranes comprising silicone hydrophobic components that allow for a high oxygen permeability in combination with hydrophilic component that allow for a limited glucose permeability (see e.g. U.S. Pat. Nos. 5,777,060, 5,882,494 and 6,642,015).